The overall objective of this proposal is to obtain an antigenc profile of human leukemic cells by using monoclonal antibodies as probes to 1) define individual antigens associated with leukemia, 2) isolate these antigens for determining their molecular profile, 3) determine the mechanisms regulating their biosynthesis, expression in the membrane and shedding, 4) define the antigenic phenotype of leukemic cells and the presence of these antigens in body fluids of leukemia patients, 5) correlate the in vitro findings with the clinical course of the disease. Several different immunization methods will be used to maximize the chances of generating hybridoma clones secreting monoclonal antibodies to the many determinants of the various molecules on the leukemic cell membrane. Specificity of the monoclonal antibodies for the leukemic state will be rigorously determined by serological reactivity with a panel of normal and transformed autologous allogeneic and xenogeneic cells. The glycoprotein or glycolipid nature and the subunit structure of the antigens detected by the monoclonal antibodies will be defined by specific radiolabeling, lectin binding and SDS-PAGE. The distribution of antigenic determinants recognized by the monoclonal antibodies will be assessed for each class of antigen in order to detect molecular heterogeneity; the chemical basis for this heterogeneity will be examined. Various agents that inhibit glycosylation, disrupt cytosketal structure and alter the differentiation state will be used to indicate how these leukemia associated antigens are integrated into the overall cellular process. It is anticipated that the knowledge generated in this study will aid our understanding of the different types of antigenic markers associated with leukemia, and provide a solid basis for future studies relating these antigens with both basic and clinical aspects of neoplasia.